Increased expression of Met protein is associated with up‐regulation of hypoxia inducible factor‐1 (HIF‐1) in tumour cells in papillary carcinoma of the thyroid

Citations Over TimeTop 10% of 2004 papers

Abstract

Met protein, the high affinity receptor for hepatocyte growth factor (HGF), was highly expressed by the tumour cells of 64 well-differentiated papillary carcinomas of the thyroid. The p145 mature form and the p170 precursor form of the protein were both isolated from the tumours. Enhanced expression of Met protein was associated with a 9.5 +/- 5-fold increase in MET RNA transcript levels, suggesting increased transcription of the gene. In the same tumours, the levels of RNA transcripts for hypoxia inducible factor-1 (HIF-1), a potent stimulator of met gene transcription, were 4.5 +/- 3-fold higher than those present in the surrounding normal thyroid tissues. HIF-1 is generally induced by hypoxia. Histological features suggestive of a hypoxia were observed in 37 of 50 tumours and included coagulative necrosis, psammoma bodies, cystic changes, intratumoural haemorrhage, and hyalinization of the fibrous stroma. Immunostaining for Met protein was particularly intense in some cells located at the tumour periphery which were characterized by an invasive phenotype. Microdissection of tumour cell nests from the invading front revealed that the levels of RNA transcripts for MET/HIF were higher than in the centre of the tumour in four of nine cases. Taken together, the findings of this study suggest that HIF-1, perhaps driven by hypoxia, may be one of the factors leading to the increased transcription of met gene in papillary carcinoma and that this event is often more pronounced at the tumour periphery.

Related Papers

• → Morphological and Histological Study on Thyroid Gland Toxicity in Male Rats Exposed to Mercury(2020)1 cited
• → The Experimental Development and Metabolism of Thyroid Gland Tumors(1955)36 cited
• I(131)使用による白鼠甲状腺機能に関する実験的研究 第1編 抗甲状腺剤，甲状腺剤，甲状腺刺戟ホルモンの白鼠甲状腺に及ぼす影響(1959)
• Susquehanna Chorale Spring Concert "Roots and Wings"(2017)
• → MORPHOFUNCTIONAL CHANGES OF THE THYROID GLAND UNDER CONDITIONS OF EXPERIMENTAL HYPOTHYROID DYSFUNCTION AND PHYSICAL EXERTION(2015)